Cadmium is a ubiquitous environmental toxicant which will induce a wide variety of deleterious effects in man and experimental animals. The major source of environmental cadmium exposure, in man, is via food intake. Cadmium toxicity, following long- or short-time exposure, has been found to be an etiological factor in various pathological processes (e.g., hypertension, testicular atrophy, cardiotoxicity and permanent lung damage). Cadmium toxicity will cause functional kidney and liver damage as evidenced by proteinuria, kidney tubular and glomerular impairment, interstitial fibrosis, anemia as well as kidney and liver cirrhosis. However, a basic understanding of the activation and/or alteration of various cellular processes caused by cadmium-induced toxicity, at the in vivo and in vitro level, remains to be clearly elucidated. Hypotheses to be tested are that cadmium-induced toxicity is potentiated by hepatic intracellular damage, the severity of damage is dependent on the time and exposure, and can be lessened by dietary zinc. The research will focus on in vivo and in vitro cadmium-induced toxicological investigations using adult male rats as the experimental model. Specific aims are to (a) develop a procedure for isolation of morphologically intact, viable, hepatic parenchymal cells in high yield after cadmium- induced toxicity, (b) determine if isolated hepatic cells will perform the metabolic processes of gluconeogenesis, glycogenolysis, glutathione release, ureogenesis and protein production, (c) determine if cadmium toxicity is lessened by dietary zinc, (d) determine if there is a time course relationship for cadmium toxicity and (e) evaluate the hepatic intracellular and intercellular aberrations, as well as organ histology and pathological consequences, caused by cadmium-induced toxicity.